The Memory Keeper’s Daughter chronicles the consequences of a father’s impulsive and immoral decision over a twenty-five-year period from March 1964 until September 1989. Dr. David Henry perpetrates a cruel and unethical medical act at the birth of his twins that sets in motion a cascade of harm. The 1964 standards of obstetrical care set a plausible context for the abandonment of a newborn without the birth mother’s knowledge. Not only could twins be unanticipated before birth, but a mother could also be completely unconscious during the birth. A blizzard that necessitates an emergency delivery in a deserted clinic provides the means and opportunity for this deception.

Dr. David Henry takes advantage of these circumstances to make his daughter born with Down syndrome disappear. The one witness is Caroline Gill, a nurse at the clinic who assists with the delivery. The first twin, Paul, emerges healthy. The second twin, Phoebe, shows the distinctive signs of Down syndrome. David gives the Phoebe to Caroline with the instructions to commit her to an institution in a neighboring city. David tells his wife Norah when she wakes up that their daughter was born dead.

Caroline duly does as she’s asked. At the ramshackle and understaffed Home for the Feebleminded, the obvious neglect and hostility repulse Caroline, and she returns to her home with Phoebe, certain that David will change his mind and accept the child into his family. Stopping for baby supplies en route, she has car trouble. Al Simpson, a kind over-the-road trucker, rescues the mother and child. The next day, Caroline confronts David, and he refuses to change the course of events he has set in motion. He alludes to the appearance of Caroline’s collusion in his ethical breach, in a way challenging her to report him, and tells her she can do what she wants with the baby.

At home, Norah’s joy over her baby son Paul can’t dispel the grief she feels over the loss of her baby daughter Phoebe whom she never met. Norah’s sister Bree suggests she organize a memorial service to achieve some closure. When Caroline sees the notice in the paper for the ceremony, she realizes that remaining in the same city and raising a baby as a single mother are not options. She has formed an attachment with Phoebe, and she decides to take her to a new city and start over.

Caroline and Phoebe move to Pittsburgh, where she answers Doro March’s ad for a companion to Doro’s ailing father. The employer relationship will become a lifelong friendship, and Phoebe has a stable home all of her life. Caroline advocates for Phoebe’s reaching her intellectual and emotional potential and helps pass landmark legislation mainstreaming children with Down syndrome into public schools. Caroline writes to David regularly about Phoebe’s progress without revealing where they live.

In Lexington, David’s practice prospers even as David and Norah’s marriage steadily disintegrates. His refusal to talk about Phoebe frustrates Norah. Hoping to open up a channel, she gives him an anniversary gift of a camera with the model name “The Memory Keeper,” which initiates David’s withdrawal into photography as a way to deal with his own sense of guilt about having given away his daughter. Motivated by loneliness and dogged by grief, Norah takes a job at a travel agency, eventually buying the business. Her world travels and late nights conceal multiple affairs. Paul becomes a musical prodigy and aspires to pursue his passion for the guitar as a career. David and Paul’s worldviews clash over facing the future, David insisting on the primacy of financial security and Paul asserting his commitment to touching and connecting with people with his performances.

David’s photography has gained him attention in the art world, and he comes to Pittsburgh for a showing of his work. Caroline sees the notice in the paper and decides to deal with her residual feelings about David by going to see him. She confesses that she was in love with him in the past, and he tells her he used that knowledge to manipulate her cooperation with disposing of his daughter. David’s grief and guilt drive him to consider suicide. Revisiting his life’s choices, he takes a trip to his abandoned family house in West Virginia, where a young pregnant woman, Rosemary, has moved in. He confesses his crime of giving away his daughter, and she reacts by not judging him. David returns to Lexington a changed man. He grants Norah a divorce, supports Paul’s plan to attend Julliard, and moves out of the family home into a duplex with Rosemary and her son Jack. Rosemary has kept his secret even while urging him to tell his wife. David uses a Pennsylvania lawyer to set up trust funds for Phoebe and Jack to be revealed upon his death.

David suddenly dies of a heart attack while running, Phoebe’s existence still unrevealed. The law firm contacts Caroline with news of David’s death and the trust fund for Phoebe. Caroline travels to Lexington, tells Norah about what happened at the birth, and gives her photos of Phoebe, now a young woman with plans to marry. Norah, Paul, and Phoebe finally meet, and Paul takes a job in Pittsburgh, looking forward to getting to know his sister.